Inhalants are a classified as central nervous system depressants that are used, and abused, for their euphoria-inducing effects, especially by adolescents. The long-term consequences ensuing from the abuse of inhalants, including toluene have received relatively little attention in the drug abuse field. One potential concern with inhalant use is the possibility of these compounds serving as a "gateway" to the abuse of other drugs. In this regard, we recently demonstrated that animals that received repeated exposure to toluene showed an enhanced motor-stimulant response to subsequent acute cocaine treatment. This sensitized behavioral response to cocaine was paralleled by an enhancement of the cocaine-induced increase in dopamine overflow in the nucleus accumbens. These data support the hypothesis that inhalants can serve as a gateway to the use and abuse of psychostimulants. The present proposal will further examine this hypothesis. Initial studies will characterize the effects of acute and repeated toluene exposure on the mesocorticolimbic dopamine system, which has been reported to play a role in drug abuse. Additional studies will further characterize the effects of repeated toluene exposure on the development of behavioral and neurochemical cross-sensitization to cocaine. A third set of studies will then determine whether repeated toluene exposure influences the acquisition of cocaine self-administration. It is hypothesized that repeated exposure to toluene alters dopamine transmission in the animal's mesocorticolimbic dopamine system in a manner similar to repeated cocaine, thereby making them more susceptible to the reinforcing properties of cocaine. The results from these studies should provide further information on the long-term consequences of inhalant use. Future studies will examine the mechanisms by which repeated toluene exposure alters mesocorticolimbic dopamine transmission.